Production of peptides

Abstract

The invention relates to a method for the production of recombinant peptides by fed-batch cultivation of a microorganism in a bioreactor containing a medium comprising organic carbon source, nitrogen source and mineral salts. The cultivation is carried out by the addition of the organic carbon source by oscillation feed and/or by oscillation variation of stirring speed, e.g. in a square or sinus wave pattern. Preferably the organic carbon source is glucose and the recombinant peptide is growth hormone.

What is claimed is:  
     
       1. Method for the production of recombinant peptide by fed-batch cultivation of a microorganism in a bioreactor containing a medium comprising organic carbon source, nitrogen source and mineral salts, wherein the cultivation is carried out by the addition of the organic carbon source in oscillation feed and/or by oscillation variation of stirring speed, without exhaustion of the organo carbon source during the oscillation period, wherein the oscillation has a wave period of from about 1 to about 30 minutes, wherein the microorganism is a biological host selected from the group consisting of bacteria, yeast and animal cell, and wherein the cultivation conditions remain aerobic. 
     
     
       2. Method according to  claim 1 , wherein the organic carbon is glucose. 
     
     
       3. Method according to  claim 1 , wherein the microorganism is  E. Coli.    
     
     
       4. Method according to  claim 1 , wherein the oscillation feed has a square wave pattern. 
     
     
       5. Method according to  claim 1 , wherein the oscillation feed has a sinus pattern. 
     
     
       6. Method according to  claim 1 , wherein the recombinant peptide is growth hormone. 
     
     
       7. Method according to  claim 1 , wherein the recombinant peptide is human growth hormone. 
     
     
       8. Method according to  claim 1 , wherein the oscillation feed has a square wave function of +/−30% of standard and a wave period of 1 minutute. 
     
     
       9. Method according to  claim 1 , wherein the oscillation feed has a wave amplitude of from about +/−5% to +/−60% of standard. 
     
     
       10. Method according to  claim 1 , wherein the oscillation variation in stirring speed +/−20% of standard with a square wave period of 1 minute. 
     
     
       11. Method according to  claim 1 , wherein the microorganism is  E. coli  and wherein the recombinant peptide is human growth hormone. 
     
     
       12. Method according to  claim 1 , wherein the recombinant peptide comprises recombinant human growth hormone, immune interferon, tissue plasminogen activator, or human insulin. 
     
     
       13. Method according to  claim 1 , wherein the oscillation feed and/or oscillation variation in stirring speed is from about +/−5% to +/−60% of standard. 
     
     
       14. Method according to  claim 2 , wherein the recombinant peptide is human growth hormone. 
     
     
       15. Method according to  claim 2 , wherein the recombinant peptide is growth hormone. 
     
     
       16. Method according to  claim 2  wherein the microorganism is  E. Coli.    
     
     
       17. Method according to  claim 2 , wherein the oscillation feed has a square wave pattern. 
     
     
       18. Method according to  claim 2 , wherein the oscillation feed has a square wave pattern. 
     
     
       19. Method according to  claim 3 , wherein the oscillation feed has a square wave pattern. 
     
     
       20. Method according to  claim 3 , wherein the oscillation feed has a sinus wave pattern. 
     
     
       21. Method according to  claim 3 , wherein the recombinant peptide is growth hormone. 
     
     
       22. Method according to  claim 3 , wherein the recombinant peptide is human growth hormone. 
     
     
       23. Method according to  claim 4 , wherein the recombinant peptide is growth hormone. 
     
     
       24. Method according to  claim 4 , wherein the recombinant peptide is human growth hormone. 
     
     
       25. Method according to  claim 5 , wherein the recombinant peptide is growth hormone. 
     
     
       26. Method according to  claim 5 , wherein the recombinant peptide is human growth hormone. 
     
     
       27. Method according to  claim 8 , wherein the oscillation variation in stirring speed is +/−20% of standard with a square wave period of 1 minute.